Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring
Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring
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DOI：
10.1096/fj.11-201194
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发表时间：
2012-10-01
期刊：
影响因子：
4.8
通讯作者：
Anderson, Diana
中科院分区：
文献类型：
--
作者：
Laubenthal, Julian;Zlobinskaya, Olga;Anderson, Diana
在人群中，孕前和产前毒物暴露与后代基因组稳定性的相关性很难分析，因为妊娠期暴露通常不能与孕前暴露分开。为了分析妊娠和受孕期间暴露对后代基因组稳定性的作用，通过彗星试验和高灵敏度半自动共聚焦激光扫描脐带血、母体血和父亲血以及来自希腊克里特岛和英国39个家庭的精子中的γ H2 AX病灶来评估稳定性。采用多元线性回归分析和后向选择，发现父亲孕前吸烟（%尾DNA：P>0.032; γ H2 AX灶：P>0.018）和母亲孕期吸烟（%尾DNA：P>0.033）在统计学上显著预测F1后代脐带血DNA损伤。母亲被动吸烟暴露未被确定为脐带血中DNA损伤的预测因子，这表明父亲吸烟的影响可能通过精子基因组传递。总之，这些研究揭示了香烟烟雾通过暴露于子宫内胎儿或父系生殖系在诱导人类F1后代DNA改变中的作用。此外，在吸烟暴露的父亲的未暴露的F1后代中鉴定出跨代DNA改变支持香烟烟雾是人类生殖细胞诱变剂的说法。Laubenthal，J.，Zlobinskaya，O.，Poterlowicz，K.，Baumgartner，A.，Gdula，M. R.，Fthenou，E.，Keramarou，M.，赫普沃思，S. J.，Kleinjans，J. C. S.，货车Schooten，F.- J.，Brunborg，G.，戈德沙尔克河W.，Schmid，T. E、安德森，D.香烟烟雾诱导的人类F1后代脐带血基因组稳定性的跨代改变FASEB J.26，3946-3956（2012）。www.fasebj.org
The relevance of preconceptional and prenatal toxicant exposures for genomic stability in offspring is difficult to analyze in human populations, because gestational exposures usually cannot be separated from preconceptional exposures. To analyze the roles of exposures during gestation and conception on genomic stability in the offspring, stability was assessed via the Comet assay and highly sensitive, semiautomated confocal laser scans of gamma H2AX foci in cord, maternal, and paternal blood as well as spermatozoa from 39 families in Crete, Greece, and the United Kingdom. With use of multivariate linear regression analysis with backward selection, preconceptional paternal smoking (% tail DNA: P>0.032; gamma H2AX foci: P>0.018) and gestational maternal (% tail DNA: P>0.033) smoking were found to statistically significantly predict DNA damage in the cord blood of F1 offspring. Maternal passive smoke exposure was not identified as a predictor of DNA damage in cord blood, indicating that the effect of paternal smoking may be transmitted via the spermatozoal genome. Taken together, these studies reveal a role for cigarette smoke in the induction of DNA alterations in human F1 offspring via exposures of the fetus in utero or the paternal germline. Moreover, the identification of transgenerational DNA alterations in the unexposed F1 offspring of smoking-exposed fathers supports the claim that cigarette smoke is a human germ cell mutagen.-Laubenthal, J., Zlobinskaya, O., Poterlowicz, K., Baumgartner, A., Gdula, M. R., Fthenou, E., Keramarou, M., Hepworth, S. J., Kleinjans, J. C. S., van Schooten, F.-J., Brunborg, G., Godschalk, R. W., Schmid, T. E., Anderson, D. Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring. FASEB J. 26, 3946-3956 (2012). www.fasebj.org